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Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation

文献类型：期刊论文

作者Xin, Jingxue1,2,3,4,12; Zhang, Hui2,12; He, Yaoxi2,4,12; Duren, Zhana5,10,11; Bai, Caijuan6; Chen, Lang1,4; Luo, Xin2,4,12; Yan, Dong-Sheng7; Zhang, Chaoyu1,4; Zhu, Xiang5
刊名NATURE COMMUNICATIONS
出版日期2020-10-01
卷号11期号:1页码:20
ISSN号2041-1723
DOI10.1038/s41467-020-18638-8
英文摘要High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation. Tibetan adaptation to the high-altitude environment represents a case of natural selection during recent human evolution. Here the authors investigated the chromatin and transcriptional landscape of umbilical endothelial cells from Tibetan and Han Chinese donors and provide genome-wide characterization of the hypoxia regulatory network associated high-altitude adaptation.
资助项目National Natural Science Foundation of China (NSFC)[91631306] ; Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)[XDA20040102] ; Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)[XDB13000000] ; NSFC[11871463] ; NSFC[61671444] ; NSFC[61621003] ; NSFC[31660308] ; Youth Innovation Promotion Association of CAS ; State Key Laboratory of Genetic Resources and Evolution[GREKF1807] ; Shanghai Municipal Science and Technology Major Project[2017SHZDZX01] ; Natural Science Foundation of Yunnan Province[2019FB042] ; NIH[P50HG007735] ; NIH[R01GM109836] ; NIH[R01HG010359]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000577113300008
出版者NATURE RESEARCH
源URL[http://ir.amss.ac.cn/handle/2S8OKBNM/52358]  
专题应用数学研究所
通讯作者Wong, Wing Hung; Wang, Yong; Su, Bing
作者单位1.Chinese Acad Sci, Acad Math & Syst Sci, CEMS, NCMIS,MDIS, Beijing 100190, Peoples R China
2.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China
3.Stanford Univ, BioX Program, Stanford, CA 94305 USA
4.Univ Chinese Acad Sci, Beijing 100101, Peoples R China
5.Stanford Univ, Dept Stat, Stanford, CA 94305 USA
6.Tibetan Univ, Sch Med, High Altitude Med Res Ctr, Lhasa 850000, Peoples R China
7.Inner Mongolia Univ, Sch Math Sci, Hohhot 010021, Peoples R China
8.Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA 94305 USA
9.Univ Chinese Acad Sci, Chinese Acad Sci, Hangzhou Inst Adv Study, Key Lab Syst Biol, Hangzhou 330106, Peoples R China
10.Clemson Univ, Ctr Human Genet, Greenwood, SC 29646 USA
推荐引用方式
GB/T 7714		 Xin, Jingxue,Zhang, Hui,He, Yaoxi,et al. Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation[J]. NATURE COMMUNICATIONS,2020,11(1):20.
APA Xin, Jingxue.,Zhang, Hui.,He, Yaoxi.,Duren, Zhana.,Bai, Caijuan.,...&Su, Bing.(2020).Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation.NATURE COMMUNICATIONS,11(1),20.
MLA Xin, Jingxue,et al."Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation".NATURE COMMUNICATIONS 11.1(2020):20.

入库方式： OAI收割

来源：数学与系统科学研究院

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